In a previous study by the same group it was shown that immunity to infection with Plasmodium falciparum can be induced experimentally in volunteers who had never had malaria through immunisation by bites of infected mosquitoes while simultaneously preventing disease with chloroquine prophylaxis. But it was unknown how long such immunity may last; 2.5 years later, the authors have completed this follow-up study.
Four of six** immune volunteers were found to be free from infection after this first attempt was made to reinfect them after 2.5 years, again via mosquito bite. Development of malaria was delayed in the remaining two immunised volunteers. More detailed analysis showed that the immune system T-cells in these immunised individuals 'remembered' the previous infection and were able to quickly clear up any re-infection. The four protected volunteers reported several mild to moderate adverse events at the time of attempted re-infection, of which the most commonly reported symptom was headache (one to three episodes per volunteer). The two patients with delayed infection had adverse events similar to those in the control group.
While encouraged by the results, the authors note several limitations to the study. These include that the same strain was used to re-infect that had been used to initially give immunity, while in the natural environment there could be genetic variation. They also note the volunteers for this study were adults, whereas most people globally are children when they are first infected.
The authors conclude: "Our simple immunisation protocol represents a blueprint for induction of sustained antimalarial immunity, providing a new technique for exploring mechanisms of immunity and highlighting new research priorities. Precedence must be given to basic understanding of mechanisms of protection in our study and those factors that inhibit protection in naturally exposed populations."
They say that further research into their method should form part of the ongoing malaria vaccine development agenda.
In a linked Comment, Dr Brian Greenwood and Dr Geoffrey Targett, London School of Hygiene & Tropical Medicine, UK, say: "If malaria immunity induced by whole parasites is very strain-specific, this could pose major problems for those working on vaccines based on this model. If, however, previous exposure to malaria is the explanation for this difference, it will be important to vaccinate early in life in endemic regions before any exposure to naturally acquired infections has happened. Challenging volunteers with a strain different from the one used to induce protection or doing immunisation and challenge studies similar to those described by Roestenberg and colleagues in malaria-exposed individuals would help to resolve which of these explanations is most probably correct."
*This period is not exactly defined but individuals require multiple naturally acquired infections over years before protected. The generally accepted paradigm is that malaria immunity is short-lived
** There were originally 10 volunteers included but 4 did not meet inclusion criteria for re-infection